Our studies of the molecular mechanisms involved in the induction of human interferon by synthetic polynucleotides have revealed this to be a clearly definable multistep process. It begins with the association of the polynucleotide-inducer with the cell membrane and culminates in the creation of cellular resistance to virus infection. The purposes of our continued research are to: 1) locate the subcellular triggering site of interferon induction by exploring the transcription of interferon mRNA in isolated nuclei and chromatin; 2) determine the critical regulatory events which control interferon production through studies in several well-defined in vitro systems; 3) purify human interferon mRNA in order to learn more about the related transcriptional and translational events; 4) synthesize radiolabeled human interferon with high specific activity suitable for physico-chemical and primary and structural studies in order to probe the important determinants of its biologic effect; 5) examine the role of cell membrane gangliosides in order to learn more about the mechanism underlying the interferon-induced cellular resistance to viral infection. We believe that new knowledge gained through these specific interferon oriented studies will provide important commentaries on the expression and regulation of genetic information in eukaryotic mammalian cells, as well as a more precise scientific rationale for the therapeutic use of human interferon.